ERAdicate S. Aureus in Patients With Bacteremia and Endocarditis (ERASE)

An Open-Label, Multiple-Ascending Dose, Multicenter Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of LSVT-1701 as an Add-on to Standard of Care Antibiotics for the Treatment of Complicated Methicillin-Sensitive and -Resistant Staphylococcus Aureus Bacteremia Including Left- and Right-sided Infective Endocarditis

This study evaluates safety and tolerability of endolysin-derived LSVT-1701 (tonabacase) as an add-on to standard of care (SOC) antibiotic therapy for the treatment of patients with complicated Staphylococcus aureus bacteremia (SAB), including left- and right-sided infective endocarditis (IE).

Study Overview

• Status: Withdrawn
• Conditions: Endocarditis Infective; Bacteremia Due to Staphylococcus Aureus; Left Sided Infective Endocarditis (Disorder); Right Sided Infective Endocarditis (Disorder)
• Intervention / Treatment: Drug: Tonabacase (LSVT-1701)

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Montana
    • Butte, Montana, United States, 59701
      • Lsvt-1701-2001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age of 18 to 90 years
• Index blood culture collection within 96 hours prior to enrollment positive for S. aureus
• Experienced at least one sign or symptom related to SAB within past 96 hours prior to enrollment
• Known or suspected left- and/or right-sided endocarditis by modified Duke criteria and/or known or suspected complicated SAB
• Required duration of SOC antibiotic therapy ≤ 42 days

Exclusion Criteria:

• Previous receipt of LSVT-1701 or CF-301 (exebacase)
• Known hypersensitivity to kanamycin or other aminoglycosides
• Treatment with any potentially effective (anti-S. aureus) systemic antibiotic for > 96 hours within 7 days before enrollment. Exception: Persistent S. aureus bacteremia after 96 hours of prior appropriate systemic antistaphylococcal antibiotic, and/or resistance to the prior systemic antibiotic
• Treatment with dalbavancin or oritavancin within the previous 90 days
• Known or suspected brain abscess or meningitis
• Community acquired pneumonia, nosocomial pneumonia because of pathogens other than S. aureus, or known polymicrobial bacteremia
• Presence of an intravascular infection source or extravascular material that cannot be removed within 96 hours after enrollment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Sequential ascending-dose cohort	Drug: Tonabacase (LSVT-1701); 4.5 or 6.0 mg/kg IV once daily for 4 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of treatment-emergent adverse events coded per the Medical Dictionary of Regulatory Activities (MedDRA) v.24.0 [norm]	Up to Day 90±14
Incidence of Grade 3 or Grade 4 toxicity according to modified DAIDS criteria version 2.1	Up to 14±4 days after end of SOC antibiotic therapy (up to Day 42)
Changes in 12-lead electrocardiogram (ECG)	Day 1 and Day 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum plasma concentration (Cmax) of LSVT-1701		Day 4
Area under the concentration-time curve (AUC) of LSVT-1701		Day 4
Overall clinical response	Overall clinical response is defined as survival, resolution or improvement of attributable signs and symptoms, no new attributable signs and symptoms, no new foci of S. aureus infection, no change in antibiotics due to non-response, and no further surgery or medical intervention to treat S. aureus.	Day 7, Day 14, after end of SOC antibiotic therapy (up to Day 42), and at test of cure (TOC; 14 days after the EOT)
Microbiological response rate		Days 3, 5, 7, 14, and up to Day 90

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall clinical response in patients with left-sided endocarditis	Overall clinical response is defined as survival, resolution or improvement of attributable signs and symptoms, no new attributable signs and symptoms, no new foci of S. aureus infection, no change in antibiotics due to non-response, and no further surgery or medical intervention to treat S. aureus.	Up to Day 14
Overall clinical response in patients with right-sided endocarditis	Overall clinical response is defined as survival, resolution or improvement of attributable signs and symptoms, no new attributable signs and symptoms, no new foci of S. aureus infection, no change in antibiotics due to non-response, and no further surgery or medical intervention to treat S. aureus.	Up to Day 14
All-cause mortality		Day 14 and Day 28
Mortality attributable to SAB		Day 14 and Day 28

Collaborators and Investigators

• Sponsor: Lysovant

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): May 1, 2022
• Primary Completion (ANTICIPATED): August 17, 2023
• Study Completion (ANTICIPATED): November 1, 2023

Study Registration Dates

• First Submitted: March 23, 2022
• First Submitted That Met QC Criteria: April 8, 2022
• First Posted (ACTUAL): April 14, 2022

Study Record Updates

• Last Update Posted (ACTUAL): June 30, 2022
• Last Update Submitted That Met QC Criteria: June 27, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: SAB; Staphylococcus aureus bacteremia; left-sided endocarditis; right-sided endocarditis
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Sepsis; Cardiovascular Infections; Disease; Bacteremia; Endocarditis, Bacterial; Endocarditis; Staphylococcal Infections
• Other Study ID Numbers: LSVT-1701-2001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No